The proposed research is a multivariate approach to understanding genetically controlled biochemical vulnerability to psychopathology, particularly to affective disorders, in ostensibly normal individuals. Platelet monoamine oxidase (MAO) activity and the red blood cell lithium/plasma lithium ratio concentration (Li ratio) are two biochemical variables which have been implicated in the pathogenesis, and perhaps genetic etiology, of bipolar illness. Genetic factors contribute to interindividual variability in each variable. Preliminary data indicate that bipolar patients have low MAO activity and higher Li ratios on the average than normal controls. We are currently studying MAO activity and the in vitro Li ratio in a large number of members of families with no family history of Major psychoses, which are serving as controls for families with one or more members with affective illness. In the course of this investigation of normal control families, we have identified the following groups of normal adult female subjects: those subjects with low MAO activity and a low in vitro Li ratio; low MAO activity and a high Li ratio; high MAO activity and a high Li ratio; high MAO activity and a high Li ratio; high MAO activity and a high Li ratio; high MAO activity and a Low Li ratio. The purpose of the proposed research is to assess differences in personality characteristics among these four groups using the Clinical Analysis Questionnaire. We will determine if subjects with low MAO activity evidence either differences in personality characteristics or a greater degree of psychopathology than those with high MAO activity and if subjects with a high Li ratio evidence difference in personality characteristics or a greater degree of psychopathology than those with a low Li ratio. We hypothesize that the greatest degree of psychopathology will be evidenced by those subjects with both low MAO activity and a high Li ratio. Evidence for such multiply determined vulnerability would indicate that a multivariate biochemical strategy is promising in denoting individuals at risk for psychiatric disturbance.